Swanson N, Abramovits W, Berman B et al.Imiquimod 2.5 and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles. J Am Acad Dermatol 62:582-590

Department of Dermatology, Oregon Health and Science University, Portland, Oregon 46032, USA.
Journal of the American Academy of Dermatology (Impact Factor: 4.45). 04/2010; 62(4):582-90. DOI: 10.1016/j.jaad.2009.07.004
Source: PubMed


The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin.
We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp.
In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment.
A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%.
Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients.
Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

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    • "A similar study by Swanson et al. [80] was done to compare efficacy of 2.5% and 3.75% cream in two 2-week cycles. Complete clearance rate with daily application was 30.6% for 2.5% cream and 35.6% for 3.75%, which would suggest that a shorter interval between applications improves outcome. "
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    ABSTRACT: Actinic keratoses (AKs) are common skin lesions heralding an increased risk of developing squamous cell carcinoma (SCC) and other skin malignancies, arising principally due to excessive ultraviolet (UV) exposure. They are predominantly found in fair-skinned individuals, and increasingly, are a problem of the immunosuppressed. AKs may regress spontaneously, remain stable or transform to invasive SCC. The risk of SCC increases for those with more than 5 AKs, and the majority of SCCs arise from AKs. The main mechanisms of AK formation are inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of cell growth and proliferation, and tissue remodeling. Human papilloma virus has also been implicated in the formation of some AKs. Understanding these mechanisms guides the rationale behind the current available treatments for AKs. One of the main principles underpinning the management of AKs is that of field cancerization. Wide areas of skin are exposed to increasing amounts of UV light and other environmental insults as we age. This is especially true for the head, neck and forearms. These insults do not target only the skin where individual lesions develop, but also large areas where crops of AKs may appear. The skin between lesions is exposed to the same insults and is likely to contain as-yet undetectable preclinical lesions or areas of dysplastic cells. The whole affected area is known as the ‘field’. Management is therefore divided into lesion-directed and field-directed therapies. Current therapies include lesion-directed cryotherapy and/or excision, and topical field-directed creams: 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy and ingenol mebutate. Combining lesion- and field-directed therapies has yielded good results and several novel therapies are under investigation. Treatment is variable and tailored to the individual making a gold standard management algorithm difficult to design. This literature review article aims to describe the rationale behind the best available therapies for AKs in light of current understanding of pathophysiology and epidemiology. A PubMed and MEDLINE search of literature was performed between January 1, 2000 and September 18, 2013. Where appropriate, articles published prior to this have been referenced. This is not a systematic review or meta-analysis, but aims to highlight the most up to date understanding of AK disease and its management. Electronic supplementary material The online version of this article (doi:10.1007/s13555-014-0049-y) contains supplementary material, which is available to authorized users.
    Full-text · Article · Mar 2014
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    • "Although it has shown good efficacy (59-84% complete clearance), a notable inflammatory response occurs during the course of treatment, which may be uncomfortable for the patient as the erythema and/or crusting may be clearly visible and may focus attention [35]. In December 2009 in Canada and then in March 2010 in USA, imiquimod 3.75% was approved for the treatment of AKs on the face or balding scalp for 2-week treatment cycles, separated by a 2-week interval without treatment [49]. These results are comparable to imiquimod 5% twice-weekly for 16 weeks, with the advantage of significantly improved patient tolerance exhibited by the lower dosage. "
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    ABSTRACT: Actinic keratoses (AK) are considered a worldwide problem with continuously increasing incidence. They clinically presents as rough or scaly plaques and are histologically characterized by a proliferation of atypical keratinocytes limited to the epidermis. AK is considered as an early step in the continuum of transformation from normal skin to invasive squamous cell carcinoma (SCC). These lesions develop on a background of field cancerization in which chronically UV- damaged-areas have accumulated molecular changes, but remain clinically normal for prolonged periods. The presence of certain clinical features of AK, such as large size, ulceration, or bleeding, suggests an increased risk of disease progression. The risk is also increased by evidence of extensive solar damage, advanced age, and immune-suppression. Many treatment modalities are available, although recent developments have focused on the management of the whole actinically damaged field. In this regard, several topical drugs have been approved, differing in efficacy, side effects, application and cost. Research is continuing aiming in the development of the "ideal" treatment which combines high clearance rates with few side effects, short treatment duration and low costs. Herein, we aim to give an overview on current treatment modalities including their mechanism of action, application scheme and common side effects. Furthermore, recent patents in the field and future aspects are discussed in this review.
    Full-text · Article · Mar 2013 · Recent Patents on Inflammation & Allergy Drug Discovery
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    • "Complete and partial (≥75% lesion reduction) clearance rates were 68.9% and 80.2%, respectively, similar to those observed after 16-week treatment courses. To investigate whether a lower concentration of imiquimod might be efficacious in the treatment of actinic keratoses with reduced adverse reactions, two placebo-controlled studies were performed comparing imiquimod 2.5% and 3.75% to the face or balding scalp for two-week or three-week cycles.22,23 Results were similar for the two trials. "
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    ABSTRACT: Imiquimod, an immune-modulating imidazoquinoline compound, has been approved in topical formulation for the treatment of actinic keratoses, superficial basal cell carcinomas, and external genital warts. Its use in the treatment of field cancerization, in particular, has been rapidly evolving. With the recent approval of a new drug application for a new concentration, as well as generic formulations, this drug has emerged at the forefront of treatment for actinic keratoses, with improved dosage scheduling and more patients having access to generic options. In the nearly 15 years since its original approval by the Food and Drug Administration for the treatment of actinic keratoses in 1997, topical imiquimod has been reviewed and studied extensively, not only for its safety and efficacy, but also for its tolerability in patients. This paper provides an indepth review of the literature, and provides clinical evidence for its inclusion in the arsenal of treatment options for patients with actinic keratoses.
    Full-text · Article · Apr 2011 · Clinical, Cosmetic and Investigational Dermatology
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